Izbicki J R, Passlick B, Hosch S B, Kubuschock B, Schneider C, Busch C, Knoefel W T, Thetter O, Pantel K
Department of Surgery, University of Munich, Germany.
J Thorac Cardiovasc Surg. 1996 Sep;112(3):623-30. doi: 10.1016/S0022-5223(96)70044-2.
The impact of lymphatic micrometastases on prognosis of non-small-cell lung cancer has not been clearly established. We therefore prospectively assessed the frequency, mode of mediastinal spread, and prognostic significance of lymphatic micrometastases in lymph nodes of 93 patients with completely resected non-small-cell lung cancer staged as pT1 to pT4 pN0 and pN1 by conventional histopathologic techniques. Frozen tissue sections from 471 lymph nodes that were staged as free of metastases by routine histopathologic examination were screened for micrometastases by the alkaline phosphatase-antialkaline phosphatase immunostaining technique with the monoclonal antibody Ber-Ep-4. Twenty of 73 patients (27.4%) with disease staged as pN0 and nine of 20 patients (45.0%) with disease staged as pN1 had nodal micrometastases. Eight of 17 patients with upper lobe primary tumors and five of 12 patients with lower lobe primary tumors exhibited skip micrometastases. Mean relapse-free survival was significantly increased in patients with pN0 disease without micrometastases (41.1 vs 29 months, p = 0.0081). In patients with pN1 disease, mean relapse-free and cancer-related survivals were also significantly increased if no micrometastases were found (34.8 and 38.2 months vs 18 and 23.5 months, p = 0.0157 and p = 0.0094). Patients with disease staged as pN0 and pN1 with micrometastases revealed no difference in cancer-related survival compared with a control population of patients with disease staged as pN2. The mode of spread was erratic. The prognosis of patients after upstaging of pN0 and pN1 disease according to results of immunohistochemical staining correlated strongly with the prognosis of patients whose disease was staged at the higher stages by conventional histopathologic examination. These findings could represent a new indication for adjuvant therapy, supporting extensive lymph node sampling for staging purposes.
淋巴微转移对非小细胞肺癌预后的影响尚未明确。因此，我们前瞻性地评估了93例经传统组织病理学技术分期为pT1至pT4、pN0和pN1且已完全切除的非小细胞肺癌患者淋巴结中淋巴微转移的频率、纵隔扩散方式及预后意义。采用碱性磷酸酶-抗碱性磷酸酶免疫染色技术及单克隆抗体Ber-Ep-4，对471个经常规组织病理学检查分期为无转移的淋巴结的冰冻组织切片进行微转移筛查。在73例分期为pN0的患者中，有20例（27.4%）存在淋巴结微转移；在20例分期为pN1的患者中，有9例（45.0%）存在淋巴结微转移。17例上叶原发性肿瘤患者中有8例、12例下叶原发性肿瘤患者中有5例出现跳跃性微转移。pN0期无微转移患者的平均无复发生存期显著延长（41.1个月对29个月，p = 0.0081）。在pN1期患者中，如果未发现微转移，平均无复发生存期和癌症相关生存期也显著延长（34.8个月和38.2个月对18个月和23.5个月，p = 0.0157和p = 0.0094）。与pN2期疾病患者的对照人群相比，pN0和pN1期有微转移的患者在癌症相关生存期方面无差异。扩散方式不稳定。根据免疫组化染色结果对pN0和pN1期疾病进行分期后患者的预后，与经传统组织病理学检查分期为更高期疾病患者的预后密切相关。这些发现可能代表辅助治疗的新指征，支持为分期目的进行广泛的淋巴结采样。
